Yasuhiro Kojima

Effect of maturation on nerve excitability in an experimental model of threshold electrotonus.

Threshold electrotonus (TE) is a new tool for investigating axonal function noninvasively in vivo. To increase its potential clinical value, we developed a rat model of TE, and examined the effects of maturation and pharmacological intervention. We recorded TE in 92 male rats (body weight 90–650 g) by stimulating the motor nerve in the tail, and applying 100‐ms conditioning currents. Motor conduction velocities increased up to a body weight of 330 g, and remained constant thereafter. TE in mature rats was similar to that in humans, and two parameters were analyzed: TEd10–20 or the mean threshold reduction 10–20 ms after the onset of the depolarizing conditioning current at 40% of threshold intensity; and TEh10–20 or the corresponding threshold decrease on hyperpolarization. Like latency, the absolute value of TEh10–20 decreased up to 330 g, and then stabilized thereafter, probably reflecting the progressive increase in the axonal diameter and relative reduction in internodal impedance. In contrast, TEd10–20 gradually decreased up to 330 g, and then jumped to a higher level, which was maintained for animals of >400 g. 4‐Aminopyridine, a blocker of fast potassium channels, selectively increased TEd10–20 only in the immature or young (<330 g) rats. This suggests that, in the mature animals, fast potassium channels become sequestrated from the nodal membrane and not activated in response to nodal depolarization. These findings indicate that mature rats (>400 g) may provide a useful experimental model for interpreting abnormal TE responses in humans, and provide evidence for nonlinear maturation of potassium channel function in myelinated axons.

An electrophysiological study of the corticospinal projections in amyotrophic lateral sclerosis.

OBJECTIVE To elucidate the pattern of corticospinal tract involvement in patients with amyotrophic lateral sclerosis (ALS), we analyzed motor evoked potential (MEP) waveforms and their relationship to the behaviour of single motor units using the peristimulus time histogram (PSTH) technique. METHODS Abnormality of the corticospinal pathways was studied in 35 ALS patients using MEPs. PSTHs were also constructed to assess the effect of magnetic cortical stimulation on the discharge pattern of a voluntarily activated motor unit. RESULTS MEPs showed a complex waveform in 10 out of 18 (56%) ALS patients with upper motor neuron signs (UMN). PSTHs revealed double primary peaks (PPs), PP1 and PP2, in 6 out of 16 motor units (38%) in ALS with UMN, as compared to only 2 out of 16 (13%) motor units in multiple sclerosis or cerebrovascular disease with UMN. None of the patients with lower motor neuron diseases or ALS without UMN had these abnormalities. The late component of complex MEPs showed a good correlation to PP2 (P < 0.0001), both probably being mediated by relatively preserved slower conducting corticospinal volleys. CONCLUSIONS These findings suggest preferential involvement of the fast conducting direct corticospinal tracts, sparing the slower or polysynaptic projections in ALS.

Chronic motor axonal neuropathy associated with antibodies monospecific for n‐acetylgalactosaminyl GD1a

We report on three patients with chronic motor neuropathy who had elevated titers of immunoglobulin (Ig)G antibodies against N‐acetylgalactosaminyl GD1a (GalNAc‐GD1a) and normal titers of antibodies against other gangliosides. Presenting with progressive muscular atrophy, fasciculations, and no sensory deficits, the patients had been diagnosed to have motor neuron disease. Electrodiagnostic features were predominantly axonal. Two patients clinically improved after intravenous Ig infusion and cyclophosphamide therapy. Increased titers of IgM antibodies to GalNAc‐GD1a were also found in two of 15 patients with multifocal motor neuropathy with conduction block but were associated with concomitant rise of anti‐GM1 antibodies. These three cases represent a chronic motor axonal neuropathy in which antibody testing for a minor ganglioside was helpful for instituting therapy.

Dynamics of a liquid crystal molecule at a solid-liquid interface detected by the time-resolved transient grating method

Abstract Dynamics of MBBA (N-(4-methoxybenzylidene)-4- n -butylaniline) in ethanol at a liquid-solid interface is selectively detected using the transient grating method with total internal reflection for probe light. The thermal grating signal decays much faster than that in bulk liquid. This faster decay is explained by the thermal conduction from the liquid to solid phase. Species grating signal from the interface also decays faster than that from the bulk liquid. The fringe length dependence of the rate constant reveals that the diffusion constant at the interface region (49 nm) is similar to that in the bulk liquid. The faster decay of the species grating is mainly attributed to the enhanced cis-trans back isomerization of MBBA at the interface.

Effect of photic conditioning on blink reflex recovery function in blepharospasm.

Patients with blepharospasm may have selective sensitivity to photic stimuli, for their symptoms are often aggravated after exposure to brightness. To investigate the pathophysiology underlying this phenomenon, we compared the effects of electric and photic conditioning on electrically-evoked blink reflex in 21 patients with blepharospasm and 11 age-matched control subjects. With electric conditioning, R1 was facilitated at inter-stimulus intervals (ISIs) of up to 100 ms in both groups. R2 was inhibited at all ISIs longer than 20 ms in the normals, but to a much lesser extent in the patients, suggesting increased excitability of the multi-synaptic reflex pathway. Compared to electric conditioning, photic conditioning was less potent in inhibiting R2 in the normals. In contrast, photic conditioning in the patients produced R2 inhibition as powerful as electric conditioning. These findings indicate that, in patients with blepharospasm, photic input has a relatively more profound inhibitory effect on the test blink reflex than electric conditioning as compared with normal subjects. The greater susceptibility of the brainstem interneurons to photic conditioning in blepharospasm may be related to the clinically-observed light sensitivity.

A case of MELAS associated with histochemical findings of muscles characteristic of MERRF

We here report a 39-year-old woman of short stature with sensorineural deafness, who suddenly developed status epilepticus. T2-weighed image of brain magnetic resonance imaging (MRI) revealed a high signal lesion in the left temporal area, the distribution of which was not compatible with any particular arterial supply. Lactate and pyruvate were elevated in the serum and cerebrospinal fluid. As the mitochondrial gene analysis revealed the m.3243A>G mutation, diagnosis of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) was made. In the histochemical study of a biopsied muscle, the intramuscular blood vessels reacted strongly with SDH (SSV), but the SSV was negative for cytochrome c oxidase (COX), the findings characteristic of myoclonic epilepsy with ragged-red fibers (MERRF). This is the first case of MELAS in which the muscle histochemistry showed positive SSV unassociated with increased COX.

Chapter 16 Preferential involvement of the fast conducting corticospinal tracts in patients with ALS

Publisher Summary Transcranial magnetic stimulation (TMS) at threshold intensity influences the discharge pattern of voluntarily activated single motor units (MUs), giving rise to a time locked synchronized firing called primary peak (PP). The analysis of the peristimulus time histograms (PSTHs) provides a physiologic measure of the corticospinal pathway in evaluating the pathophysiology of upper motor neuron diseases. This chapter discusses a study in which all amyotrophic lateral sclerosis (ALS) patients eventually fulfilled the EI-Escorial criteria for ALS. Based on the clinical findings at the time of the study, they were classified into groups of 26 typical ALS patients with upper and lower motor neuron signs, four patients with primary lateral sclerosis (ALS-PLS) with predominantly UMN and five patients with progressive muscular atrophy (ALS-PMA) with exclusive lower motor neuron signs. The threshold for cortical excitation was determined at rest using the oscilloscope display at a sensitivity of 50 μV/vertical division. In ALS with upper motor neuron (UMN), PSTHs frequently show double PPs and transcranial magnetic stimulation (TMS) elicits a high threshold motor evoked potentials (MEP) with a complex waveform. In the patients under observation, PP 2 usually matches the late component of complex MEP in latency. In contrast, normal subjects or patients without UMN show no such abnormalities.